کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1949725 | 1537783 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Lipid bodies in oxidized LDL-induced foam cells are leukotriene-synthesizing organelles: a MCP-1/CCL2 regulated phenomenon
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کلمات کلیدی
CysLTsCOXsadipose differentiation related proteinoxLDLCC chemokine receptor 2ADRPCCR2LTScPLA2i.p.Cysteinyl leukotrienesERKLPSMCP-1/CCl2 - MCP-1 / CCl2Atherosclerosis - آترواسکلروز(تصلب شریان)Arachidonic acid - اسید آراشیدونیکinflammation - التهاب( توروم) interleukin - اینترلوکینFlap - برآافزا intraperitoneal - داخل صفاقیFoam cell - سلول فومCyclooxygenases - سیکلوکوکسی ...Platelet-activating factor - فاکتور فعال کننده پلاکتcytosolic phospholipase A2 - فسفولیپاز A2 سیتوزولlipid droplet - قطره چربیLeukotrienes - لکوتری هاLeukotriene - لکوترینlipoxygenase - لیپواکسیژنازoxidized low density lipoprotein - لیپوپروتئین با چگالی کم اکسید شدهlipopolysaccharide - لیپوپلی ساکاریدMacrophage - ماکروفاژ map - نقشهwild type - نوع وحشیPAF - نیروی هوایی پاکستانmitogen-activated protein - پروتئین فعال mitogenextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Lipid-laden foam macrophages are emerging as key players in early atherogenesis. Even though cytoplasmic lipid bodies (lipid droplets) are now recognized as organelles with cell functions beyond lipid storage, the mechanisms controlling lipid body biogenesis within macrophages and their additional functions in atherosclerosis are not completely elucidated. Here we studied oxLDL-elicited macrophage machinery involved in lipid body biogenesis as well as lipid body roles in leukotriene (LT) synthesis. Both in vivo and in vitro, oxLDL (but not native LDL) induced rapid assembly of cytoplasmic lipid bodies-bearing ADRP within mice macrophages. Such oxLDL-elicited foamy-like phenotype was a pertussis toxin-sensitive process that depended on a paracrine activity of endogenous MCP-1/CCL2 and activation of ERK. Pretreatment with neutralizing anti-MCP-1/CCL2 inhibited macrophage ADRP protein expression induced by oxLDL. By directly immuno-localizing leukotrienes at their sites of synthesis, we showed that oxLDL-induced newly formed lipid bodies function as active sites of LTB4 and LTC4 synthesis, since oxLDL-induced lipid bodies within foam macrophages compartmentalized the enzyme 5-lipoxygenase and five lipoxygenase-activating protein (FLAP) as well as newly formed LTB4 and LTC4. Consistent with MCP-1/CCL-2 role in ox-LDL-induced lipid body biogenesis, in CCR2 deficient mice both ox-LDL-induced lipid body assembly and LT release were reduced as compared to wild type mice. In conclusion, oxLDL-driven foam cells are enriched with leukotriene-synthesizing lipid bodies - specialized organelles whose biogenic process is mediated by MCP-1/CCL2-triggered CCR2 activation and ERK-dependent downstream signaling - that may amplify inflammatory mediator production in atherosclerosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1791, Issue 11, November 2009, Pages 1066-1075
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1791, Issue 11, November 2009, Pages 1066-1075
نویسندگان
Adriana R. Silva, Patricia Pacheco, Adriana Vieira-de-Abreu, Clarissa M. Maya-Monteiro, Barbara D'Alegria, Kelly G. Magalhães, Edson F. de Assis, Christianne Bandeira-Melo, Hugo C. Castro-Faria-Neto, Patricia T. Bozza,